The Picornaviridae is the smallest animal RNA virus known in the art, and it has 7 genera, i.e., rhinovirus genus, enterovirus genus, aphthovirus genus, cardiovirus genus, hepatovirus genus, double ECHOviruses (enteric cytopathic human orphan viruses) genus, and some unclassified picornaviruses. Picornaviruses can induce diseases in many systems, such as respiratory diseases, hand-foot-mouth diseases, meningitis/encephalitis, acute poliomyelitis, cardiovascular diseases, hemorrhagic conjunctivitis, and hepatitis.
In the late 1980s, virology developed greatly. Several important events in viral life cycle have been well described, and many molecular targets are confirmed. In recent years, the appearance of many novel antiviral drugs also promotes the development of virology. The activities of picornavirus inhibitors are studying. These inhibitors act on targets including viral capsid protein 1 (VP1), a relatively conservative capsid structure for mediating viral absorption/uncoating process. VP1s of viruses of different serotypes are of highly conservative structure, but are very important for replication of viruses, and inhibitors acting on this target could be drugs for combating picornaviruses, among which Pirodavir is a typical representative (ANTIMICROBIAL AGENTS and CHEMOTHERAPY, 36(4), 727-732), and this compound exhibits significant activity against rhinovirus (HRV) in vivo and in vitro. Bioorg Med. Chem. 2009, 17: 621-624 discloses a series of compounds with good inhibition activity to HRV, among which the compounds 4-{2-[N-(3-chloropyridazin-4-yl)piperidin-4-yl]ethoxyl}benzoic acid ethyl ester (5f) and 3,6-dichloro-4-{4-[2-(4-ethoxylphenoxy)ethyl]piperazin-1-yl}pyridazine (5c) have an activity comparable to Pirodavir, but have a relatively low toxicity, and a relatively high index of selectivity.
However, there is still need to develop an antiviral agent having a novel structure, effectiveness, and optionally one or more physiological and/or physicochemical advantages.